Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

OBJECTIVE: Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. METHODS: Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. RESULTS: In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. CONCLUSIONS: This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Systemic knockout of Tmem175 results in aberrant differentiation but no effect on hematopoietic reconstitution.

Lysosomes play crucial roles in regulating cell metabolism, and K+ channels are critical for controlling various aspects of lysosomal function. Additionally, lysosomal activity is essential for maintaining the quiescence of hematopoietic stem cells (HSCs) under both steady-state and stress conditions. Tmem175 is a lysosomal potassium channel protein. To further investigate the role of K+ channels in HSCs, our study employed knockout mice to examine the function of Tmem175. Our research findings demonstrate that the deletion of Tmem175 does not disrupt the functionality of HSCs in both stable and stressed conditions, including irradiation and intraperitoneal 5-FU injections. However, we did observe that the absence of Tmem175 impairs the long-term differentiation capacity of HSCs into myeloid differentiated subpopulation cells（In this paper, it is referred to simply as M cells）in HSC transplantation test, while promoting their differentiation into T cells. This suggests that Tmem175 plays a role in the lineage differentiation of HSCs without being essential for their self-renewal or long-term regenerative capabilities.

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Dysregulated neural activity between the thalamus and cerebral cortex mediates cortical reorganization in cervical spondylotic myelopathy.

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM.

Longitudinal multidiversity pattern and the environmental drivers of riparian bird communities along submontane rivers of Changbai Mountains, China.

Riparian zones are biodiversity hotspots in montane ecosystems and are of critical conservation concern. However, studies on longitudinal diversity patterns and environmental drivers have been restricted to aquatic fauna, while the animals that rely on both river and riparian resources have been of much less concern. Here, we examined the multifaceted diversity distribution of riparian birds along longitudinal gradients and analyzed the importance of environmental factors in shaping these patterns in the Changbai Mountains. Hump-shaped relationships between elevation and taxonomic, phylogenetic, and functional diversity, as well as with the conservation value index, were evident along each of the classic submontane rivers. Forest cover, vegetation height variation, and land cover patches positively affected the taxonomic diversity indices. In addition to the species richness, fluvial geomorphology variables (river sinuosity and gravel bar) were significantly related to the phylogenetic diversity. However, there was no statistical evidence for a relationship between functional diversity and the environmental variables examined. This study emphasized the necessity of including multiple diversity measures beyond taxonomic diversity and demonstrated the importance of both terrestrial and aquatic components in shaping the multifaceted biodiversity pattern of riparian organisms living in riparian zones. The results suggested that conservation priority should be given to both rivers and banks in the middle reaches and that riparian birds could be good candidate indicators of environmental change in the submontane river-forest ecotone.

Effect of sex on the gut microbiota characteristics of passerine migratory birds.

The gut microbiota, considered the "invisible organ" in the host animal, has been extensively studied recently. However, knowledge about the gut microbiota characteristics of passerine migratory birds during migration is limited. This study investigated the gut microbiota characteristics of three dominant migratory bird species (namely orange-flanked bluetail Tarsiger cyanurus, yellow-throated bunting Emberiza elegans, and black-faced bunting Emberiza spodocephala) in the same niche during spring migration and whether they were bird sex-specific. The compositions of gut microbiota species in these three migratory bird species and their male and female individuals were found to be similar. The main bacterial phyla were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, and the main genera were Lactobacillus, Acinetobacter, Rickettsiella, and Mycobacterium; however, their relative abundance was different. Moreover, some potential pathogens and beneficial bacteria were found in all the three bird species. Alpha diversity analysis showed that in T. cyanurus, the richness and diversity of the gut microbiota were higher in male individuals than in female individuals, while the opposite was true for E. elegans and E. spodocephala. The alpha diversity analysis showed significant differences between male and female individuals of E. elegans (p < 0.05). The beta diversity analysis also revealed that the gut microbial community structure differed significantly between the male and female individuals of the three migratory bird species.

mTORC2 Facilitates Liver Regeneration Through Sphingolipid-Induced PPAR-α-Fatty Acid Oxidation.

BACKGROUND & AIMS: During liver regeneration after partial hepatectomy, the function and metabolic pathways governing transient lipid droplet accumulation in hepatocytes remain obscure. Mammalian target of rapamycin 2 (mTORC2) facilitates de novo synthesis of hepatic lipids. Under normal conditions and in tumorigenesis, decreased levels of triglyceride (TG) and fatty acids (FAs) are observed in the mTORC2-deficient liver. However, during liver regeneration, their levels increase in the absence of mTORC2. METHODS: Rictor liver-specific knockout and control mice underwent partial hepatectomy, followed by measurement of TG and FA contents during liver regeneration. FA metabolism was evaluated by analyzing the expression of FA metabolism-related genes and proteins. Intraperitoneal injection of the peroxisome proliferator-activated receptor α (PPAR-α) agonist, p53 inhibitor, and protein kinase B (AKT) activator was performed to verify the regulatory pathways involved. Lipid mass spectrometry was performed to identify the potential PPAR-α activators. RESULTS: The expression of FA metabolism-related genes and proteins suggested that FAs are mainly transported into hepatocytes during liver regeneration. The PPAR-α pathway is down-regulated significantly in the mTORC2-deficient liver, resulting in the accumulation of TGs. The PPAR-α agonist WY-14643 rescued deficient liver regeneration and survival in mTORC2-deficient mice. Furthermore, lipidomic analysis suggested that mTORC2 deficiency substantially reduced glucosylceramide (GluCer) content. GluCer activated PPAR-α. GluCer treatment in vivo restored the regenerative ability and survival rates in the mTORC2-deficient group. CONCLUSIONS: Our data suggest that FAs are mainly transported into hepatocytes during liver regeneration, and their metabolism is facilitated by mTORC2 through the GluCer-PPAR-α pathway, thereby establishing a novel role for mTORC2 in lipid metabolism.

Binding affinity and conformation of a conjugated AS1411 aptamer at a cationic lipid bilayer interface.

Aptamers have been widely used in the detection, diagnosis, and treatment of cancer. Owing to their special binding affinity toward cancer-related biomarkers, aptamers can be used for targeted drug delivery or bio-sensing/bio-imaging in various scenarios. The interfacial properties of aptamers play important roles in controlling the surface charge, recognition efficiency, and binding affinity of drug-delivering lipid-based carriers. In this research, the interfacial behaviors, such as surface orientation, molecular conformation, and adsorption kinetics of conjugated AS1411 molecules at different cationic lipid bilayer interfaces were investigated by sum frequency generation vibrational spectroscopy (SFG-VS) in situ and in real-time. It is shown that the conjugated AS1411 molecules at the DMTAP bilayer interface show a higher binding affinity but with slower binding kinetics compared to the DMDAP bilayer interface. The analysis results also reveal that the thymine residues of cholesteryl conjugated AS1411 molecules show higher conformational ordering compared to the thymine residues of the alkyl chain conjugated AS1411 molecules. These understandings provide unique molecular insight into the aptamer-lipid membrane interactions, which may help researchers to improve the efficiency and safety of aptamer-related drug delivery systems.

The gut microbiota of bats confers tolerance to influenza virus (H1N1) infection in mice.

Pathogens from wild animals cause approximately 60% of emerging infectious diseases (EIDs). Studies on the immune systems of natural hosts are helpful for preventing the spread of EIDs. Bats are natural hosts for many emerging infectious pathogens and have a unique immune system that often coexists with pathogens without infection. Previous studies have shown that some genes and proteins may help bats fight virus infection, but little is known about the function of the bat gut microbiome on immunity. Here, we transplanted gut microbiota from wild bats (Great Himalayan Leaf-nosed bats, Hipposideros armiger) into antibiotic-treated mice, and found that the gut microbiota from bats regulated the immune system faster than mice after antibiotic treatment. Moreover, we infected mice with H1N1, and found that the gut microbiota of bats could effectively protect mice, leading to decreased inflammatory response and increased survival rate. Finally, metabolomics analysis showed that the gut microbiota of bats produced more flavonoid and isoflavones. Our results demonstrate that the quick-start innate immune response endowed by bat gut microbiota and the regulatory and antiviral effects of gut microbiota metabolites successfully ensured mouse survival after viral challenge. To our knowledge, our study was the first to use fecal microbiota transplantation (FMT) to transplant the gut microbiota of bats into mice, and the first to provide evidence that the gut microbiota of bats confers tolerance to viral infections.

Interfacial Complexation Induced Controllable Fabrication of Stable Polyelectrolyte Microcapsules Using All-Aqueous Droplet Microfluidics for Enzyme Release.

Water-in-water (w/w) emulsions are particularly advantageous for biomedical-related applications, such as cell encapsulation, bioreactors, biocompatible storage, and processing of biomacromolecules. However, due to ultralow interfacial tension, generation and stabilization of uniform w/w droplets are challenging. In this work, we report a strategy of creating stable and size-controllable w/w droplets that can quickly form polyelectrolyte microcapsules (PEMCs) in a microfluidic device. A three-phase (inner, middle, outer) aqueous system was applied to create a stream of inner phase, which could be broken into droplets via a mechanical perturbation frequency, with size determined by the stream diameter and vibration frequency. The interfacial complexation is formed via electrostatic interaction of polycations of poly(diallyldimethylammoniumchloride) with polyanions of polystyrene sodium sulfate in the inner and outer phases. With addition of negatively charged silica nanoparticles, the stability, permeability, and mechanical strength of the PEMC shell could be well manipulated. Prepared PEMCs were verified by encapsulating fluorescein isothiocyanate-labeled dextran molecules and stimuli-triggered release by varying the pH value or osmotic pressure. A model enzyme, trypsin, was successfully encapsulated into PEMCs and released without impairing their catalytic activity. These results highlight its potential applications for efficient encapsulation, storage, delivery, and release of chemical, biological, pharmaceutical, and therapeutic agents.

Complete mitochondrial genome of Pallas's Leaf Warbler (Phylloscopus proregulus).

In the present study, the complete mitochondrial DNA sequence of Pallas's Leaf Warbler (Phylloscopus proregulus) was determined for the first time. The mitochondrial genome of Pallas's Leaf Warbler is a circular molecule of 16,880 bp in size and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 control regions. The base composition is 32.7% for C, 14.3% for G, 30.0% for A and 23.0% for T. These data will be useful for studying the genetic diversity within the species of Pallas's Leaf Warbler and phylogenetic relationships among different Phylloscopidae species.

Complete mitochondrial genome of the Salangid icefish Neosalanx taihuensis (Actinopterygii: Osmeriformes: Salangidae).

The complete mitochondrial DNA genome of the Salangid icefish (Neosalanx taihuensis) was sequenced by the primer walking sequence method. The entire mitochondrial genome of this species is 17,035 bp in length, making it the longest among the reported mitochondrial genomes of Osmeriformes. It contains 13 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region (CR). The gene arrangement, nucleotide composition, and codon usage pattern of the mitochondrial genome are similar to those of other teleosts except for two long tandem repeats in the CR. A 486 bp tandem repeat fragment was identified that comprises 2 copies of 243 bp motif and accounts approximately 35.5% of the CR. The 243 bp tandem repeat motif can be folded into a stem-loop secondary structure. Phylogenetic analysis based on 12 concatenated protein-coding genes of the heavy strand shows the genus Neosalanx diverged most recently and clustered with Protosalanx hyalocranius as a clade.

Complete mitochondrial genome sequence of Chestnut-flanked white-eye (Zosterops erythropleurus).

The Chestnut-flanked white-eye (Zosterops erythropleurus) is a species of family Zosteropidae, which is distributed widely in the world. In the present study, the complete mitochondrial genome sequence of Chestnut-flanked white-eye was determined. It has a total length of 17 811 bp, and contains 13 protein-coding genes, 22 tRNA genes, 2 ribosome RNA genes and 2 control regions. The total base composition was 30.2% for A, 31.0% for C, 14.2% for G and 24.6% for T. The phylogenetic tree of Chestnut-flanked white-eye and 13 other species belonging to the order Passeriformes was built. The molecular data presented here will be useful to study the evolutionary relationships and genetic diversity of Chestnut-flanked white-eye.

The complete sequence of mitochondrial genome of Siberian accentor (Prunella montanella).

The Siberian accentor, Prunella montanella (Passeriformes, Prunellidae), is a small passerine bird. In this study, the complete mitochondrial genome sequence of Siberian accentor was determined. It has a total length of 16 832 bp, and contains 13 protein coding genes, 22 tRNA genes, two ribosome RNA genes, and one control region. The nucleotide composition is 30.1% for A, 31.0% for C, 15.0% for G and 23.9% for T, respectively. The overall GC content is lower than AT. The phylogenetic tree of Siberian accentor and 10 other species belonging to order Passeriformes was built. The DNA data presented here will be useful to study the evolutionary relationships and genetic diversity of Siberian accentors.

3,5-Dicarb-oxy-2,6-dimethyl-pyridinium chloride dihydrate.

In the title compound, C(9)H(10)NO(4) (+)·Cl(-)·2H(2)O, both the cation and the anion have crystallographic twofold rotation symmetry; in the former, one N and one C atom lie on the rotation axis. In the crystal structure, the ions and water mol-ecules are linked via O-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonds into layers parallel to (101).

4-Methyl-morpholinium bromide.

The six-membered ring in the title salt, C(5)H(12)NO(+)·Br(-), has a chair conformation. In the crystal, the cations are linked to the anions by N-H⋯Br hydrogen bonds.

2,4-Dimethyl-anilinium chloride.

In the crystal structure of the title compound, C(8)H(12)N(+)·Cl(-), all H atoms bonded to the ammonium N atom are hydrogen bonded to the chloride ions, with N⋯Cl distances in the range 3.080 (2)-3.136 (2) Å, resulting in 16-membered macrocyclic rings involving four formula units of the title compound.

Dimethyl 1-(3-cyano-benz-yl)-1H-pyrazole-3,5-dicarboxyl-ate.

In the mol-ecule of the title compound, C(15)H(13)N(3)O(4), the dihedral angle between the pyrazole and benzene ring planes is 67.7 (1)°. The crystal structure is stabilized by an intra-molecular C-H⋯O hydrogen bond and two weak inter-molecular C-H⋯O inter-actions.

Dimethyl 1-(2-cyano-benz-yl)-1H-pyrazole-3,5-dicarboxyl-ate.

In the mol-ecule of the title compound, C(15)H(13)N(3)O(4), the dihedral angle between the pyrazole and benzene rings is 79.89 (6)°. An intra-molecular C-H⋯O hydrogen bond is present. The crystal structure is stabilized by π-π stacking inter-actions between centrosymmetrically related pyrazole rings with a centroid-centroid distance of 3.500 (3) Å.